Periosteal Manifestations of Osteomyelitis and Arthritis on Ultrasound: A Systematic Review.

Ultrasound (US) can visualize the periosteal changes in the early stage compared to radiography. In this review, we studied periosteal manifestations on US and assessed their diagnostic utility for osteomyelitis (OM) and arthritis. We included articles that studied ultrasonographic findings of periosteal changes in OM and arthropathies with aims to systematically review periosteal manifestations of each condition and summarize diagnostic values of each finding. A total of 13 articles were included in the systematic review. Of these, 10 articles are on OM, 3 articles are on psoriatic arthritis (PsA), 1 article is on rheumatoid arthritis (RA), and 1 article is on gouty arthritis (GA). In OM, subperiosteal fluid/subperiosteal collection (SF/SC) was detected in 32%-76% within 72 h after presentation. Periosteal reaction (PR) was seen after day 4 and the sensitivity on US ranges from 33% to 100%. In PsA, PR was seen near 16%-59% in active PsA joints. Periosteal changes are rarely detected in RA joints. Small hyperechoic spots were seen in 87.5% of GA. SF/SC may be seen on US as the earliest sign followed by PR for OM. PR is more specific in PsA than RA. Further investigations on periosteal abnormalities on US are warranted to confirm our findings.

Bone Fragility in Hereditary Connective Tissue Disorders: A Systematic Review and Meta-Analysis.

OBJECTIVE: To investigate bone fragility in patients with hereditary connective tissue disorders (HCTD), including Ehlers-Danlos syndrome (EDS), Marfan's syndrome (MFS) and Loeys-Dietz syndrome (LDS). METHODS: From inception to June 2022, potentially eligible studies were identified in the Medline and EMBASE databases using search strategy that included terms for "HCTD", "Fracture" and "Osteoporosis". Eligible studies must consist of a group of patients with HCTD and report prevalence/incidence of fracture/osteoporosis in their participants, with or without comparison with healthy individuals. Point estimates with standard errors were obtained from each study and combined using the generic inverse variance method. RESULTS: Among the 4206 articles identified, 19 studies were included. The pooled prevalence of fracture in EDS, MFS, and LDS were 44% (95% confidence interval [CI], 25% to 65%, I2 88%), 17% (95% CI, 11% to 26%, I2 68%), 69% (95% CI, 47% to 85%, I2 83%), respectively. The pooled prevalence of osteoporosis in EDS was 17% (95% CI, 8% to 34%, I2 96%). EDS was associated with fracture [pooled odds ratio {OR} 4.90 (95% CI, 1.49 - 16.08, I2 86%)], but not osteoporosis [pooled OR 1.34 (95% CI, 0.28 - 6.36, I2 87%). One study reported a 5% (95% CI, 3% to 8%) prevalence of osteoporosis in MFS, which was associated with fracture [incidence rate ratio 1.35 (95% CI, 1.18 - 1.55)] and osteoporosis [subhazard ratio 3.97 (95% CI, 2.53 - 6.25)]. CONCLUSION: EDS was associated with fracture, which could be independent of osteoporosis status. MFS had a milder degree of increased risk of fracture and osteoporosis. Despite no data from cohort studies, there was a significantly higher rate of fracture in LDS.

Long-Term Safety Profiles of Macrolides and Tetracyclines: A Systematic Review and Meta-Analysis.

Macrolides and tetracyclines are antibiotics that have a range of anti-inflammatory properties beyond their microbial capabilities. Although these antibiotics have been in widespread use, the long-term safety profiles are limited. We performed a systematic review and meta-analysis of randomized clinical trials that compared macrolides or tetracyclines with placeboes to provide long-term safety information. We searched Medline and EMBASE from inception to October 2022 and identified studies that reported study drug-related death, serious adverse events (SAEs), or withdrawal rates, and common adverse effects of each drug. Relative risk (RR) and number needed to harm were calculated. Of the 52 randomized clinical trials included, there are 3151 participants on doxycycline, 2519 participants on minocycline, 3049 participants on azithromycin, 763 participants on clarithromycin, 262 participants on erythromycin, and 100 participants on roxithromycin. There was no death related to any study drugs and rates of SAE were not significantly different from placebo in any drug. Overall withdrawal rates were slightly higher than placebo in doxycycline (RR, 1.30; 95% CI, 1.12-1.52) and minocycline (RR, 1.29; 95% CI, 1.15-1.46). Withdrawal rates due to adverse events were higher in doxycycline (RR, 2.82; 95% CI, 1.88-4.22), minocycline (RR, 1.48; 95% CI, 1.09-1.98), and azithromycin (RR, 1.53; 95% CI, 1.13-2.08). Gastrointestinal disturbances are the most common tolerable adverse effects for every drug. Photosensitivity and rash are the second most common adverse effects for doxycycline and minocycline. We found no evidence that long-term use up to 2 years of macrolides or tetracyclines was associated with increased risk of SAEs.

Catabolic mediators from TLR2-mediated proteoglycan aggrecan peptide-stimulated chondrocytes are reduced by Lactobacillus-conditioned media.

In osteoarthritis (OA), extracellular matrix (ECM) digestion by cartilage-degrading enzymes drives cartilage destruction and generates ECM fragments, such as proteoglycan aggrecan (PG) peptides. PG peptides have been shown to induce immunological functions of chondrocytes. However, the role of PG peptides in stimulating catabolic mediators from chondrocytes has not been investigated. Therefore, we aim to determine the effects and its mechanism by which PG peptides induce chondrocytes to produce catabolic mediators in OA. Human chondrocytes were stimulated with IFNγ and various PG peptides either (i) with or (ii) without TLR2 blockade or (iii) with Lactobacillus species-conditioned medium (LCM), a genus of bacteria with anti-inflammatory properties. Transcriptomic analysis, cartilage-degrading enzyme production and TLR2-intracellular signaling activation were investigated. Chondrocytes treated with PG peptides p16-31 and p263-280 increased expression levels of genes associated with chondrocyte hypertrophy, cartilage degradation and proteolytic enzyme production. TLR2 downstream signaling proteins (STAT3, IkBα and MAPK9) were significantly phosphorylated in p263-280 peptide-stimulated chondrocytes. MMP-1 and ADAMTS-4 were significantly reduced in p263-280 peptides-treated condition with TLR2 blockade or LCM treatment. Phosphorylation levels of IkBa, ERK1/2 and MAPK9 were significantly decreased with TLR2 blockade, but only phosphorylation levels of MAPK9 was significantly decreased with LCM treatment. Our study showed that PG peptide stimulation via TLR2 induced cartilage-degrading enzyme production via activation of MAPK, NFκB and STAT3 pathways.

Urate-lowering therapy is associated with a reduced risk of arrhythmias: a systematic review and meta-analysis.

Objective: While urate-lowering therapy (ULT) is linked to increased cardioprotective benefits on primary prevention of cardiovascular events such myocardial infarction or heart failure, little is known regarding their effects on arrhythmia risk. The purpose of this study was to investigate the relationship between incident arrhythmias and ULT. Methods: We searched MEDLINE and Embase from inception to May 2023. Included studies were randomized controlled trials and cohort studies that compared the risk of cardiac arrhythmias among ULT users with non-ULT users. Results: A total of 12,420 patients from five studies were analyzed, comprising 7,359 subjects in the ULT group and 5,061 subjects in the non-ULT group. Our results showed that ULT users had significant reductions in the risk of arrhythmias (pooled relative risk [RR] 0.82, 95% confidence interval [CI] 0.74~0.92, p<0.001, I2=0.0%) compared to non-ULT users. Subgroup analysis did not show that ULT users had a significant reduced risk of atrial fibrillation (pooled RR 0.76, 95% CI 0.54~1.05, p=0.096 with I2=15.4%) compared to non-ULT users. Conclusion: ULT is associated with lower risk of overall arrhythmias. Further studies are warranted to confirm our findings.

Increased Risk of Systemic Lupus Erythematosus in Patients with Chronic Urticaria: A Systematic Review and Meta-analysis.

Introduction: The association between systemic lupus erythematosus (SLE) and chronic urticaria (CU) has been suggested in the literature although the amount of evidence is still relatively limited. We aimed to combine all available studies on this association using systematic review and meta-analysis technique. Methods: Potentially eligible studies were identified from Medline and EMBASE from inception to February 2023 using search strategy that comprised of terms for "chronic urticaria" and "systemic lupus erythematosus". The eligible study must consist of one group of patients with CU and another group of comparators without CU and must compare the prevalence of SLE in each group and report effect size with 95% confidence intervals (95% CIs). We extracted such data from each study to calculate a pooled odds ratio using the generic inverse variance method with random-effect model. Funnel plot was used to evaluate publication bias. Newcastle-Ottawa Scale was used to appraise the methodological quality of the included studies. Results: A total of 5,155 articles were identified. After two rounds of independent review by four investigators, five studies met the eligibility criteria and were included in the meta-analysis. The meta-analysis found an increased prevalence of SLE among patients with CU compared with individuals without CU with the pooled odds ratio of 5.03 (95% CI, 2.57-9.85, I2 of 93%). Conclusion: This systematic review and meta-analysis found that patients with CU had a significantly increased risk of SLE compared to individuals without CU.

Lupus Cardiomyopathy and Nephritis Associated With Adalimumab and Cytomegalovirus Infection in a Patient With Seronegative Rheumatoid Arthritis: A Case of Rhupus Syndrome.

Tumor necrosis factor-alpha (TNF-α) inhibitors are associated with lupus-like disease, known as anti-TNF-α-induced lupus (ATIL). Cytomegalovirus (CMV) was reported to exacerbate lupus in the literature. To date, systemic lupus erythematosus (SLE) triggered by adalimumab in the setting of CMV infection has never been described. We present an unusual case of a 38-year-old female with a past medical history of seronegative rheumatoid arthritis (SnRA) who developed SLE associated with the use of adalimumab and CMV infection. She had severe SLE features including lupus nephritis and cardiomyopathy. The medication was discontinued. She was initiated on pulse steroid therapy and discharged with an aggressive regimen for SLE, including prednisone, mycophenolate mofetil, and hydroxychloroquine. She remained on the medications until a year later upon follow-up. ATIL from adalimumab usually manifests only mild symptoms of SLE such as arthralgia, myalgia, and pleurisy. Nephritis is very rare, and cardiomyopathy is unprecedented. Concomitant CMV infection might contribute to disease severity. Patients with SnRA may have an increased risk of developing SLE later when exposed to such medications and infection.

Role of antimicrobial peptides in atopic dermatitis.

Host defense peptides (HDPs) or antimicrobial peptides (AMPs) are short cationic amphipathic peptides of divergent sequences, which are part of the innate immune system and produced by various types of cells and tissues. The predominant role of HDPs is to respond to and protect humans against infection and inflammation. Common human HDPs include defensins, cathelicidin, psoriasin, dermcidin, and ribonucleases, but these peptides may be dysregulated in the skin of patients with atopic dermatitis (AD). Current evidence suggests that the antimicrobial properties and immunomodulatory effects of HDPs are involved in AD pathogenesis, making HDPs research a promising area for predicting disease severity and developing novel treatments for AD. In this review, we describe a potential role for human HDPs in the development, exacerbation, and progression of AD and propose their potential therapeutic benefits.

Hospital epidemiology and antimicrobial susceptibility of isolated methicillin-resistant Staphylococcus aureus: a one-year retrospective study at a tertiary care center in Thailand.

BACKGROUND: Increased rates of Staphylococcus aureus resistance and its morbidity and mortality have raised concern about the strategy of antibiotic use. OBJECTIVES: This study aimed to determine the prevalence of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) isolates among Thai patients with S. aureus infection and to identify risk factors and appropriate antibiotics for these resistant strains. METHODS: Data of culture-proven S. aureus isolates from clinical specimens during 2017 in King Chulalongkorn Memorial Hospital, Thailand, were retrospectively collected and classified as methicillin-sensitive S. aureus or MRSA by cefoxitin screening and oxacillin minimum inhibitory concentration by the Vitek 2 system. Each isolate was also tested for susceptibility to teicoplanin, erythromycin, clindamycin, linezolid, trimethoprim/sulfamethoxazole, ciprofloxacin, moxifloxacin, tetracycline, doxycycline, and vancomycin by Vitek 2. Demographic information and comorbidities from medical records were reviewed to identify risk factors for S. aureus infection. RESULTS: MRSA isolates were identified in 147 (17%) of 890 patients with no different ratio in adults or children. A higher proportion of MRSA in hospital-acquired settings was observed (27% vs. 12%; p < 0.001). Comorbidities significantly associated with MRSA were chronic lung, cardiovascular, and neurological diseases. Atrial fibrillation, dementia, and benign prostatic hyperplasia were independently associated with MRSA isolation. Vancomycin was still susceptible to all kinds of infection. One VRSA isolate was from colonization. CONCLUSION: The prevalence of MRSA in our facility seemed to be comparatively low. Vancomycin is still an appropriate option for MRSA coverage since all S. aureus isolates in our center were sensitive to vancomycin. However, careful attention is warranted since one colonization isolate was VRSA.